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Publication : An immunohistochemical atlas of necroptotic pathway expression.

First Author  Chiou S Year  2024
Journal  EMBO Mol Med Volume  16
Issue  7 Pages  1717-1749
PubMed ID  38750308 Mgi Jnum  J:361147
Mgi Id  MGI:7855996 Doi  10.1038/s44321-024-00074-6
Citation  Chiou S, et al. (2024) An immunohistochemical atlas of necroptotic pathway expression. EMBO Mol Med 16(7):1717-1749
abstractText  Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators - Caspase-8, RIPK1, RIPK3 and MLKL - in formalin-fixed mouse and human tissues. We observed surprising heterogeneity in protein expression within tissues, whereby short-lived immune barrier cells were replete with necroptotic effectors, whereas long-lived cells lacked RIPK3 or MLKL expression. Local changes in the expression of necroptotic effectors occurred in response to insults such as inflammation, dysbiosis or immune challenge, consistent with necroptosis being dysregulated in disease contexts. These methods will facilitate the precise localisation and evaluation of necroptotic signaling in vivo.
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